cDNA microarray technologies have enabled one to obtain comprehensive profiles of gene expression in normal versus malignant cells (Perou, C. M. et al., Nature. 406: 747-752, 2000; Clark, E. A. et al., Nature. 406: 532-535, 2000; Okabe, H. et al., Cancer Res. 61: 2129-2137, 2001). This approach discloses the complex nature of cancer cells, and helps to improve understanding of carcinogenesis. Identification of genes that are deregulated in tumors can lead to more precise and accurate diagnosis of individual cancers, and to development of novel therapeutic targets (Golub, T. R. et al., Science 286: 531-537, 1999).
Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide. In spite of recent progress in therapeutic strategies, prognosis of patients with advanced HCC remains very poor. Although molecular studies have revealed that alterations of TP53, CTNNB1 and/or AXIN1 genes can be involved in hepatocarcinogenesis (Perou, C. M. et al., Nature. 406: 747-752, 2000; Satoh, S. et al., Nat. Genet. 24: 245-250, 2000), these changes appear to be implicated in only a fraction of HCCs. Accordingly, a ultimate gene that can be a novel diagnostic marker and/or drug target for treatment of cancers has been desired.
The present inventors previously reported that a novel gene, VANGL1, was identified by genome-wide analysis of HCCs (Yagyu, R. et al., International Journal of Oncology 20: 1173-1178, 2002).